Pragmatic clinical trials offer important benefits, such as generating evidence that is suited to inform real-world health care decisions and increasing research efficiency. However, PCTs also present ethical challenges. One such challenge involves the management of information that emerges in a PCT that is unrelated to the primary research question, yet may have implications for the individual patients, clinicians, or health care systems from whom or within which research data were collected. We term these findings as?pragmatic clinical trial collateral findings,? (...) or?PCT-CFs?. In this article, we explore the ethical considerations associated with the identification, assessment, and management of PCT-CFs, and how these considerations may vary based upon the attributes of a specific PCT. Our purpose is to map the terrain of PCT-CFs to serve as a foundation for future scholarship as well as policy-making and to facilitate careful deliberation about actual cases as they occur in practice. (shrink)

The ethical principle of ‘respect for persons’ in clinical research has traditionally focused on protecting individuals’ autonomy rights, but respect for participants also includes broader, although less well understood, ethical obligations to regard individuals’ rights, needs, interests and feelings. However, there is little empirical evidence about how to effectively convey respect to potential and current participants. To fill this gap, we conducted exploratory, qualitative interviews with participants in a clinical genomics implementation study. We interviewed 40 participants in English or Spanish (...) about their experiences with respect in the study and perceptions of how researchers in a hypothetical observational study could convey respect or a lack thereof. Most interviewees were female, identified as Hispanic/Latino or non-Hispanic white, reported annual household income under US$60 000 and did not have a Bachelor’s degree ; 30% had limited health literacy. We identified four key domains for demonstrating respect: personal study team interactions, with an emphasis on empathy, appreciation and non-judgment; study communication processes, including following up and sharing results with participants; inclusion, particularly ensuring materials are understandable and procedures are accessible; and consent and authorisation, including providing a neutral informed consent and keeping promises regarding privacy protections. While the experience of respect is inherently subjective, these findings highlight four key domains that may meaningfully demonstrate respect to potential and current research participants. Further empirical and normative work is needed to substantiate these domains and evaluate how best to incorporate them into the practice of research. (shrink)

Medical ethics assumes a clear boundary between clinical research and clinical medicine: one produces knowledge for the benefit of future patients, while the other provides optimal care to individuals right now. It also assumes that the two cannot be integrated without sacrificing the needs of the current patient to those of future patients. But integration could allow us to provide better care to everyone, now and in the future.

Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain (...) principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals. (shrink)

Pragmatic trials aim to directly inform health care decision-making through the collection of so-called ‘real world data’ from observations of comparative treatment effects in clinical practice. In order to ensure the applicability and feasibility of a pragmatic trial, design features may be necessary that deviate from standard research ethics requirements. Examples are traditional requirements to seek written informed consent and to perform extensive data and safety monitoring. Proposals for deviations from standard research ethics practice have resulted in controversy about their (...) ethical acceptability. One of the justifications for altered procedures is the allegedly high social value of pragmatic trials. In order to properly operationalize the concept in the ethical assessment of pragmatic trial designs, specification is warranted. We identified three determinants from common claims about a pragmatic trial's social value: the extent to which the research question has real world relevance, the trial design's ability to generate a real world answer and the probability of direct uptake of the results by decision-makers in practice. Subsequently, we discuss how these determinants should be applied to the practice of pragmatic trials, and to what extent they might be applicable to explanatory trials. (shrink)